High aldehyde dehydrogenase activity enhances stem cell features in breast cancer cells by activating hypoxia-inducible factor-2α
High aldehyde dehydrogenase activity enhances stem cell features in breast cancer cells by activating hypoxia-inducible factor-2α
复制标题
DOI：
10.1016/j.canlet.2012.11.026
复制
发表时间：
2013-06-01
期刊：
影响因子：
9.7
通讯作者：
Nam, Jeong-Seok
中科院分区：
文献类型：
--
作者：
Kim, Ran-Ju;Park, Jeong-Ran;Nam, Jeong-Seok
高乙醛脱氢酶（ALDH）活性已被认为是乳腺癌中癌症干细胞（CSC）的标志物。在这项研究中，我们检查了 ALDH 活性的抑制是否会抑制 4T1 同基因小鼠乳腺癌模型中的干细胞样特性。我们发现 ALDH 阳性 4T1 细胞在体外和体内表现出干细胞样特性。阻断 ALDH 活性可减少乳腺癌细胞系中 CSC 的生长。用 ALDH 抑制剂二乙氨基苯甲醛 (DEAB) 治疗小鼠可显着抑制 4T1 细胞向肺的转移。最近的证据表明 ALDH 会影响干细胞对缺氧的反应；因此，我们研究了 ALDH 与乳腺癌缺氧信号之间的可能联系。缺氧诱导因子 2 α (HIF-2 α) 在 ALDH 阳性 4T1 细胞中高度失调。我们观察到 ALDH 与乳腺癌细胞系和组织中的 HIF-2 α 表达高度相关。 DEAB 处理乳腺癌细胞可在体外降低 HIF-2 α 的表达。此外，HIF-2α表达的减少抑制了ALDH阳性4T1细胞的体外自我更新能力和体内肿瘤起始。因此，我们的研究结果可能为探索乳腺癌治疗的新策略提供必要的证据。 (C) 2012 Elsevier Ireland Ltd. 保留所有权利。
High aldehyde dehydrogenase (ALDH) activity has been recognized as a marker of cancer stem cells (CSCs) in breast cancer. In this study, we examined whether inhibition of ALDH activity suppresses stem-like cell properties in a 4T1 syngeneic mouse model of breast cancer. We found that ALDH-positive 4T1 cells showed stem cell-like properties in vitro and in vivo. Blockade of ALDH activity reduced the growth of CSCs in breast cancer cell lines. Treatment of mice with the ALDH inhibitor diethylaminobenzaldehyde (DEAB) significantly suppressed 4T1 cell metastasis to the lung. Recent evidence suggests that ALDH affects the response of stem cells to hypoxia; therefore, we examined a possible link between ALDH and hypoxia signaling in breast cancer. Hypoxia-inducible factor-2 alpha (HIF-2 alpha) was highly dysregulated in ALDH-positive 4T1 cells. We observed that ALDH was highly correlated with the HIF-2 alpha expression in breast cancer cell lines and tissues. DEAB treatment of breast cancer cells reduced the expression of HIF-2 alpha in vitro. In addition, reduction of HIF-2 alpha expression suppressed in vitro self-renewal ability and in vivo tumor initiation in ALDH-positive 4T1 cells. Therefore, our findings may provide the evidence necessary for exploring a new strategy in the treatment of breast cancer. (C) 2012 Elsevier Ireland Ltd. All rights reserved.